| | TOP STORY | iPSC-Derived β Cells Model Diabetes Due to Glucokinase Deficiency
To determine whether stem cell-derived β cells recapitulate molecular-physiological phenotypes of a diabetic subject, scientists generated induced pluripotent stem cells (iPSCs) from subjects with maturity-onset diabetes of the young type 2, which is characterized by heterozygous loss of function of the gene encoding glucokinase. [J Clin Invest] Full Article | Press Release
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| | PUBLICATIONS (Ranked by impact factor of the journal) | Induction of a Hemogenic Program in Mouse Fibroblasts
Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. Researchers attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. They identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6, that efficiently induces endothelial-like precursor cells, with the subsequent appearance of hematopoietic cells. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release
Immunologic and Chemical Targeting of the Tight-Junction Protein Claudin-6 Eliminates Tumorigenic Human Pluripotent Stem Cells
Investigators identified the tight-junction protein Claudin-6 as a cell-surface-specific marker of human pluripotent stem cells that can be used to selectively remove Claudin-6-positive cells from mixed cultures. They showed that Claudin-6 is absent in adult tissues but highly expressed in undifferentiated cells, where it is dispensable for human pluripotent stem cell survival and self-renewal. [Nat Commun] Abstract Stimulation of Somatic Cell Reprogramming by Eras-Akt-Foxo1 Signaling Axis
The authors report that a tumor- or embryonic stem cell (ESC)-specific Ras gene ERas, which encodes a constitutively active form of GTPase, and its downstream Phosphoinositide-3 kinase/Akt signaling pathway are important facilitators for the somatic reprogramming process. They found that overexpression of ERas retrovirally enhanced mouse induced pluripotent stem cell induction while ERas knockdown repressed it. [Stem Cells] Abstract | Full Article
Defined Extracellular Matrix Components Are Necessary for Definitive Endoderm Induction
Soluble differentiation factors are known to increase extracellular matrix (ECM) expression, yet ECM's ability to direct embryonic stem cell (ESC) fate is not well understood. To address the extent to which these proteins regulate differentiation when assembled into a matrix, researchers examined mouse ESC embryoid bodies and found that their ability to maintain pluripotency marker expression was impaired by soluble serum fibronectin. [Stem Cells] Abstract
Modeling Dravet Syndrome Using Induced Pluripotent Stem Cells (iPSCs) and Directly Converted Neurons
Investigators established iPSC lines from one severe myoclonic epilepsy of infancy (SMEI, also known as Dravet Syndrome) patient and one genetic epilepsy with febrile seizures plus patient, respectively. Functional glutamatergic neurons were subsequently differentiated from these iPSCs. [Hum Mol Genet] Abstract
Maturation and Function of Human Embryonic Stem Cell-Derived Pancreatic Progenitors in Macroencapsulation Devices following Transplant into Mice
Scientists previously demonstrated that human embryonic stem cell-derived pancreatic progenitor cells matured under the kidney capsule in a mouse model of diabetes into glucose-responsive insulin-secreting cells capable of reversing diabetes. However, the formation of cells resembling bone and cartilage was a major limitation of that study. Therefore, they developed an improved differentiation protocol that aimed to prevent the formation of off-target mesoderm tissue following transplantation. [Diabetologia] Abstract HMGN1 Modulates Nucleosome Occupancy and DNase I Hypersensitivity at the CpG Island Promoters of Embryonic Stem Cells
Researchers showed that HMGN1, a nucleosome binding protein ubiquitously expressed in vertebrate cells, preferentially binds to CpG island-containing promoters, and affects the organization of nucleosomes, DNaseI hypersensitivity, and the transcriptional profile of mouse embryonic stem cells and neural progenitors. [Mol Cell Biol] Abstract | Full Article The Epigenetic Modifier Ubiquitin Specific Protease 22 (Usp22) Regulates Embryonic Stem Cell Differentiation via Transcriptional Repression of Sex Determining Region Y-box 2 (Sox2)
The authors report that the histone ubiquitin hydrolase Usp22 is a critical epigenetic modifier that controls this transition from self-renewal to differentiation. Usp22 is induced as embryonic stem cells differentiate and is necessary for differentiation into all three germ layers. [J Biol Chem] Abstract | Full Article  |
| | POLICY NEWS | US Supreme Court Rules Patents on ‘Natural’ Human Genes Invalid
In one of the most anxiously awaited court decisions of the year, the US Supreme Court unanimously struck down patents on isolated, natural human genes. Patents on synthesized DNA, however, are still valid, the justices said. Included in that category are commercially important patents on cDNA - segments of DNA synthesized using an RNA template. [Supreme Court, United States] Press Release | Syllabus
UK Scientists Fear Further Cuts
Chancellor of the Exchequer George Osborne is set to unveil the next comprehensive spending review, which sets spending for government departments. He said that he hoped to make clear the government’s “long-term commitment” to research in the new review, but scientists fear another budget freeze. [Chancellor of the Exchequer, United Kingdom] Press Release Japan Eyes U.S. National Institutes of Health as Model for a New Agency
Japan's government may create its own version of the U.S. National Institutes of Health to foster medical innovation and bridge the gap between the laboratory and the clinic. [Japanese Government, Japan]
Press Release Protestors to Government: 'Save Spanish Science'
Spanish researchers arrived at a closed gate at the Ministry of Economy and Competitiveness in Madrid, where they had wanted to deliver a clear message to their government: Save Spanish science. Protestors carried a 10-point wish list, signed by 45,000 supporters, that includes increasing public spending for research to 2% of the gross domestic product by 2016, improving opportunities for young researchers, and creating an independent funding agency. [Ministry of Economy and Competitiveness, Spain] Press Release |
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